Okadaic acid disrupts Golgi structure and impairs enzyme synthesis and secretion in the rat pancreas

Waschulewski, Ingo H.; Kruse, Marie‐Luise; Agricola, Brigitte; Kern, H.; Schmidt, W.

doi:10.1152/ajpgi.1996.270.6.g939

Cited by 11 publications

(13 citation statements)

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“…Besides, 8% of the genes altered after the 3 h OA treatment were related to cellular transport processes. OA was previously found to interfere in the secretion of newly synthesized proteins and exocytosis in rats [45]; both effects could be related to the expression alterations found in the present study.…”

Section: Resultssupporting

confidence: 67%

“…Similar to the 3 h OA treatment, an important number of these genes are involved in metabolism including electron transport chain, but also a great percentage of genes related to translation were observed. The expression alterations found in the genes involved in processes of translation and transcription might be related to the previously reported OA-induced inhibition of protein synthesis [45,46]. …”

Section: Resultsmentioning

confidence: 58%

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Identification of differentially expressed genes in SHSY5Y cells exposed to okadaic acid by suppression subtractive hybridization

Valdiglesias¹,

Fernández‐Tajes²,

Pásaro³

et al. 2012

BMC Genomics

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BackgroundOkadaic acid (OA), a toxin produced by several dinoflagellate species is responsible for frequent food poisonings associated to shellfish consumption. Although several studies have documented the OA effects on different processes such as cell transformation, apoptosis, DNA repair or embryogenesis, the molecular mechanistic basis for these and other effects is not completely understood and the number of controversial data on OA is increasing in the literature.ResultsIn this study, we used suppression subtractive hybridization in SHSY5Y cells to identify genes that are differentially expressed after OA exposure for different times (3, 24 and 48 h). A total of 247 subtracted clones which shared high homology with known genes were isolated. Among these, 5 specific genes associated with cytoskeleton and neurotransmission processes (NEFM, TUBB, SEPT7, SYT4 and NPY) were selected to confirm their expression levels by real-time PCR. Significant down-regulation of these genes was obtained at the short term (3 and 24 h OA exposure), excepting for NEFM, but their expression was similar to the controls at 48 h.ConclusionsFrom all the obtained genes, 114 genes were up-regulated and 133 were down-regulated. Based on the NCBI GenBank and Gene Ontology databases, most of these genes are involved in relevant cell functions such as metabolism, transport, translation, signal transduction and cell cycle. After quantitative PCR analysis, the observed underexpression of the selected genes could underlie the previously reported OA-induced cytoskeleton disruption, neurotransmission alterations and in vivo neurotoxic effects. The basal expression levels obtained at 48 h suggested that surviving cells were able to recover from OA-caused gene expression alterations.

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Section: Resultssupporting

confidence: 67%

Section: Resultsmentioning

confidence: 58%

Identification of differentially expressed genes in SHSY5Y cells exposed to okadaic acid by suppression subtractive hybridization

Valdiglesias¹,

Fernández‐Tajes²,

Pásaro³

et al. 2012

BMC Genomics

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“…The first involves the cytoskeleton and functional structures that depend on it. For example, MCYST-LR along with another microorganism-derived protein phosphatase inhibitor, okadaic acid, were shown to block the transport of proteins from the endoplasmic reticulum to the Golgi apparatus in mammalian cells (Davidson et al, 1992;Davidson and Balch, 1993) and, at least for okadaic acid, lead to a time-dependent Golgi fragmentation (Waschlulewski et al, 1996). Inasmuch as the Golgi complex is the origin of lysosomes, lysosomal membranes might be similarly prone to disintegration.…”

Section: Discussionmentioning

confidence: 99%

Microcystin-LR induced cellular effects in mammalian and fish primary hepatocyte cultures and cell lines: A comparative study

2006

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“…For instance, we don't believe that syncollin functions directly in protein biosynthesis as a pancreas-specific accelerator of synthesis rates. Pancreatic synthesis rates are known to be reduced under a variety of adverse conditions, such as energy depletion (42) and a block in secretion or intracellular transport (25,47). Syncollin is specifically localized to the lumen of the zymogen granule membrane (2), whereas it would need to operate in the rough endoplasmic reticulum if it were involved in controlling protein synthesis rates.…”

Section: Discussionmentioning

confidence: 99%

Loss of the Zymogen Granule Protein Syncollin Affects Pancreatic Protein Synthesis and Transport but Not Secretion

Antonin¹,

Wagner

Riedel³

et al. 2002

Molecular and Cellular Biology

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Syncollin is a small protein that is abundantly expressed in pancreatic acinar cells and that is tightly associated with the lumenal side of the zymogen granule membrane. To shed light on the hitherto unknown function of syncollin, we have generated syncollin-deficient mice. The mice are viable and show a normal pancreatic morphology as well as normal release kinetics in response to secretagogue stimulation. Although syncollin is highly enriched in zymogen granules, no change was found in the overall protein content and in the levels of chymotrypsin, trypsin, and amylase. However, syncollin-deficient mice reacted to caerulein hyperstimulation with a more severe pancreatitis. Furthermore, the rates of both protein synthesis and intracellular transport of secretory proteins were reduced. We conclude that syncollin plays a role in maturation and/or concentration of zymogens in zymogen granules.The exocrine pancreas is specialized for the synthesis, storage, and release of digestive proenzymes. Since the pancreas exhibits the highest rate of protein synthesis among all mammalian tissues (8), it has served for many years as the model system for the study of intracellular protein transport and secretion (31). In pancreatic acinar cells, secretory proteins are synthesized at the rough endoplasmic reticulum and transported to the Golgi apparatus. In the trans-Golgi network, proteins are segregated into condensing vacuoles that undergo further maturation to zymogen granules (for a review, see reference 37). During maturation and condensation, granular content proteins are segregated from proteins destined for constitutive secretion (for a review, see references 3 and 43). Mature granules are stored in the apical pole of the acinar cell. Upon nervous or hormonal stimulation, a selective rise in the local Ca 2ϩ concentration is observed in the apical pole, which triggers exocytotic discharge of the granule content into the pancreatic duct (32).Formation, maturation, and exocytosis of zymogen granules are multistep processes that are only incompletely understood at the molecular level. For instance, it is largely unknown how zymogens are sorted in the trans-Golgi network and how they are packaged and concentrated in zymogen granules. Furthermore, the molecular steps involved in granule docking and fusion still need to be elucidated. As in many other intracellular fusion events, members of the Rab and SNARE (for soluble N-ethylmaleimide sensitive factor attachment protein receptor) protein families were shown to be involved in pancreatic secretion (16,18,29,30,44), but how they are regulated and which proteins are involved in transmitting the calcium signal to the exocytotic machinery are still unknown.

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Okadaic acid disrupts Golgi structure and impairs enzyme synthesis and secretion in the rat pancreas

Cited by 11 publications

References 0 publications

Identification of differentially expressed genes in SHSY5Y cells exposed to okadaic acid by suppression subtractive hybridization

Identification of differentially expressed genes in SHSY5Y cells exposed to okadaic acid by suppression subtractive hybridization

Microcystin-LR induced cellular effects in mammalian and fish primary hepatocyte cultures and cell lines: A comparative study

Loss of the Zymogen Granule Protein Syncollin Affects Pancreatic Protein Synthesis and Transport but Not Secretion

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